Diagnosis of Fetal Abnormalities during the First Trimester.

The quality of prenatal diagnosis of fetal abnormalities has advanced with improved resolution of ultrasound imaging and cytogenetic/molecular analysis. In this article, we briefly review the history of diagnosing fetal abnormalities and the current status of prenatal diagnosis during the first trimester (up to the first 14 weeks' gestation), focusing especially on fetal malformations and chromosomal abnormalities. As for detectable morphological abnormalities, roughly half of all major structural anomalies including those in the central nervous system, cardiovascular system and gastrointestinal system can be detected, if not definitely diagnosed. For screening of chromosomal abnormalities, especially for trisomy 21, ultrasound soft markers such as increased nuchal translucency, maternal serum markers and their combinations have been implemented. More recently, non-invasive prenatal testing, by analyzing cell-free DNA in maternal serum, is now available to detect chromosomal abnormalities with higher predictability. Although invasive chorionic villus sampling offers definite diagnosis for chromosomal abnormalities during the first trimester, non-invasive diagnostic techniques are patient-friendly and promising in the future perspectives on prenatal diagnosis for chromosomal abnormalities.

[Analysis of prenatal follow-up strategies for trisomy 21 affected pregnancies in France]. / Analyse du parcours de dépistage prénatal des femmes ayant donné naissance en France à un enfant atteint de trisomie 21.

OBJECTIVE: The main objective of this study was to screen the prenatal follow-up of women with live birth trisomy 21 child in order to evaluate the proportion of prenatal screening failure versus cases where the women refused either the screening or the prenatal diagnosis of Down syndrome. This study covers the period of time from 2009 to 2012 when the national prenatal screening policy changed from second to first trimester and allows for a comparative assessment of the nationwide efficiency of the various maternal serum marker based strategies. METHOD: All authorized cytogenetic laboratories sent required data for all cases of trisomy 21 diagnosed in FRANCE in new-borns (less than 1-year-old) from January 2010 to July 2013. RESULTS: A total of 1253 cases of trisomy 21 were diagnosed before 1 year of age whose mother did not had prenatal diagnosis. For 861 of them, information on the prenatal follow-up was available, with 72% of cases where a prenatal screening was organized either by maternal serum marker or by ultrasound. Results of the screening strategy was positive with maternal serum marker in 28% of cases (calculated risk≥1/250), positive because of abnormal ultrasound in 5% and negative with maternal marker screening (whatever the strategy used) in 67% of cases. Detection rate over the period of the study was 82%, with similar efficiency of first and second trimester strategies (83%) but significantly lower with sequential association of first trimester Nuchal translucency measurement and second trimester serum screening (70%). CONCLUSION: Switching from second trimester to first trimester screening strategy, with as many trisomy 21 foetuses diagnosed with half invasive procedures fulfilled national health policy objectives. Analysis of these data gives useful insights to elaborate a future screening policy involving cell-free foetal DNA sequencing.

Associations between maternal serum free beta human chorionic gonadotropin (ß-hCG) levels and adverse pregnancy outcomes.

The objective was to determine the strength of relationship between maternal free beta human chorionic gonadotropin (ß-hCG) concentrations and rates of adverse pregnancy outcomes. Consecutive records of the database of our Down screening project were assessed for free ß-hCG levels and pregnancy outcomes. Pregnancies with foetal chromosomal or structural anomalies and those with underlying disease were excluded. Free ß-hCG levels of < 0.5, > 0.5 and < 2.0, and ≥ 2.0 MoM were categorised as low, normal and high, respectively. Of 17,082 screened women, 13,620 were available for analysis. In the first trimester (n = 8150), low ß-hCG levels significantly increased risk for intrauterine growth restriction (IUGR), preterm birth, low birth weight (LBW) and low Apgar score with relative risk of 1.66, 1.43, 1.83 and 2.89; whereas high ß-hCG group had a significant decreased risk of preterm birth and GDM with relative risk of 0.73 and 0.62. In the second trimester (n = 5470), both low and high ß-hCG groups had significant increased risks of the most common adverse outcomes, i.e. spontaneous abortion, IUGR and preterm birth. In conclusion, abnormally low (< 0.5MoM) or high (> 2.0 MoM) free ß-hCG levels are generally associated with an increased risk of adverse pregnancy outcomes. Nevertheless, high free ß-hCG levels in the first trimester may possibly decrease risk of preterm delivery and GDM.

A study on the regional parameters of triple screening model of Down syndrome in the second trimester in Jinhua City / 预防医学

Objective To explore the regional parameters of triple screening model of Down syndrome in the second trimester in Jinhua City.Methods A total of 20 232 second trimester pregnant women with single fetus (gestational age at 15 -20 +6 weeks)was enrolled,and their serum samples were determined by American Perkin Elmer company Auto DELFIA automatic time -resolved fluorescence immunoassay analyzer for Down syndrome screening with triple markers, namely AFP,free β-hCG and uE3 .The risks of Down syndrome were evaluated by Lifecycle 3.2 software.And the risks of Down syndrome were re -calculated by local statistical median equations.Pregnant women were suggested to receive amniotic fluid fetal karyotype analysis if the risk of Down syndrome were equal or above 1 /270.Results Local median marker levels were significantly higher than the software built -in median levels (P <0.01).Both true -positive detection rates (sensitivity)were 87.50%.The false positive rate of local median equations was 4.24%,while the built -in median equations was 4.74%.Conclusion There are significant differences on the race and region by using the LifeCycle 3.2 median equations.The local equations may lower the false positive rate.

Second trimester maternal serum inhibin-A in fetal anemia secondary to hemoglobin Bart's disease.

OBJECTIVE: To compare the levels of inhibin-A between pregnancies with fetal anemia secondary to Hb Bart's disease and pregnancies with normal non-anemic fetuses. METHODS: Sixty-five pregnancies at risk of fetal Hb Bart's disease scheduled for cordocentesis at 18-22 weeks were prospectively recruited into the study. Inhibin-A levels were measured from maternal blood drawn before cordocentesis. Fetal blood samples were collected for fetal Hb typing and hemoglobin (Hb) levels. RESULTS: Maternal serum inhibin-A was significantly higher in women with fetal Hb Bart's disease than those with unaffected fetuses (1.03 MoM (multiple of median) and 0.75 MoM, respectively, p = 0.001). The relationship between maternal serum inhibin-A and fetal Hb level was a quadratic equation; inhibin-A = 5.248 - 9.415(Hb) + 4.919(Hb)(2) (r(2) = 0.274, p < 0.001). Maternal serum inhibin-A did not correlate with cardiomegaly but was significantly associated with placental thickness; inhibin-A = 1.372 - 0.751(Pl) + 0.214(Pl)(2) (r(2) = 0.237, p = 0.007). CONCLUSIONS: Maternal serum inhibin-A levels were significantly higher in pregnancies with fetal Hb Bart's disease. The elevation of inhibin-A was likely to be a consequence of fetal anemia and placentomegaly. Since inhibin-A is commonly used as a component of quadruple test; the calculated risk of Down's syndrome may be unreliable in pregnancies with fetal Hb Bart's disease or possible fetal anemia.

Multivariate Analysis of Adverse Pregnancy Outcome by Multiprediction Factors / 대한산부인과학회잡지

PURPOSE: To evaluate a role as over 35 years, maternal serum markers, and a false positive screen for Down syndrome were the predictor of adverse pregnancy outcome. Materials and METHODS: From Mar.1994, through Feb.1996, 5284 women were screened triple test to detect Down syndrome in the second trimester and were delivered Samsung Cheil hospital. The values of each maternal serum markers were measured with radioimmunoassay. And then, the screen positive of Down syndrome was calculated using alpha-software Version 4.0. The adverse outcome of the fetus and the mother included low birth weight(LBW) ( 2.0 MoM) associated with IUFD, LBW, PIH, prematurity, and PPROM , elevated MS-hCG (>3.0 MoM) associated with IUFD, LBW, PIH, prematurity, and placenta previa, lowered uE3 (0.05) CONCLUSIONS: Some predictors such as over 35 year, elevated hCG, lowered uE3, a false positive screen for Down syndrome were significantly associated with adverse pregnancy outcome. Also in multivariate analysis, we identified especially elevated AFP to be the most reliable predictor for adverse pregnancy outcome.